Stimulation of arachidonic acid release and prostaglandin synthesis by bryostatin 1.

Abstract

The mechanism of tumor promotion may involve stimulation of prostaglandin production. Previous studies with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) have identified two effects of TPA on prostaglandin production. TPA stimulates both arachidonic acid release and de novo synthesis of prostaglandin H synthase. Activation of protein kinase C by TPA appears to be part of the mechanism to cause arachidonic acid release. However, it is unclear if induction of prostaglandin H synthase also involves activation of protein kinase C. Bryostatin 1 is known to activate protein kinase C and to mimic some of the effects of TPA. We compared bryostatin 1 with TPA for the ability to cause arachidonic acid release and induce synthesis of prostaglandin H synthase. Bryostatin 1 induced arachidonic acid release and caused some prostaglandin production but only marginally induced synthesis of prostaglandin H synthase. Furthermore, we found that bryostatin 1 could inhibit the effect of TPA both in stimulation of arachidonic acid release and in the induction of prostaglandin H synthase.